TRIMPEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIMPEX (TRIMPEX).
Inhibits dihydrofolate reductase, blocking the conversion of dihydrofolic acid to tetrahydrofolic acid, thereby inhibiting bacterial thymidine synthesis and DNA replication.
| Metabolism | Primarily hepatic via N-oxidation and hydroxylation; not extensively metabolized by cytochrome P450 enzymes. |
| Excretion | Renal: 40-70% as unchanged drug; biliary/fecal: minimal (10-15% as metabolites) |
| Half-life | 8-11 hours; prolonged in renal impairment (creatinine clearance <10 mL/min: 20-40 hours) |
| Protein binding | 42-46% primarily to albumin |
| Volume of Distribution | 1.5-2 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 90-100% |
| Onset of Action | Oral: 2-4 hours; intravenous: 30 minutes to 1 hour |
| Duration of Action | 12-24 hours; extended by renal impairment or concurrent CYP450 inhibition |
| Molecular Weight | 290.32 |
5 mg/kg orally every 6 hours for acute infections; 5 mg/kg orally every 12 hours for chronic urinary tract infections.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: administer every 8-12 hours; CrCl <10 mL/min: administer every 12-24 hours. |
| Liver impairment | No specific adjustment for Child-Pugh A or B; Child-Pugh C: reduce dose by 50% or extend interval to every 12 hours. |
| Pediatric use | 2.5 mg/kg orally every 12 hours for children <2 months; 5 mg/kg orally every 6 hours for children ≥2 months. Maximum 400 mg/day. |
| Geriatric use | Use with caution; consider renal function. Adjust dose based on CrCl; monitor for myelosuppression and folate deficiency. |
| 1st trimester | Avoid; animal studies show teratogenic effects (skeletal and visceral malformations) and no adequate human studies. |
| 2nd trimester | Avoid; risk of kernicterus in the newborn due to displacement of bilirubin from albumin binding sites. |
| 3rd trimester | Avoid; risk of kernicterus in the newborn and hemolytic anemia in G6PD-deficient infants. |
Clinical note
Comprehensive clinical and safety monograph for TRIMPEX (TRIMPEX).
| Placental transfer | Trimethoprim crosses the placenta readily, achieving fetal serum concentrations approximately equal to maternal serum concentrations. |
| Breastfeeding | Trimethoprim is excreted into breast milk in low amounts (milk:plasma ratio ~0.5-1.0). However, there is a theoretical risk of kernicterus in neonates, especially those with G6PD deficiency, hyperbilirubinemia, or prematurity. The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised in ill or premature infants. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to trimethoprim or any componentMegaloblastic anemia due to folate deficiencySevere hepatic impairmentSevere renal impairment (CrCl <15 mL/min) without monitoring
| Precautions | May cause megaloblastic anemia due to folate deficiency, especially in patients with marginal folate levels, Risk of blood dyscrasias (thrombocytopenia, leukopenia, neutropenia); monitor CBCs, Caution in patients with impaired hepatic or renal function, May aggravate porphyria, Geriatric patients may be at increased risk of severe adverse reactions |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, spinach, salt substitutes) due to risk of hyperkalemia. Trimethoprim may reduce folate absorption, so ensure adequate dietary folate (leafy greens, legumes) or supplement if needed. Take with food to minimize GI upset. |
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| Lactation Rating | L2 (Safer) according to LactMed; however, some sources consider it 'Moderate Risk' due to potential for bilirubin displacement. |
| Teratogenic Risk | Trimpex (trimethoprim) is a folate antagonist. First trimester: risk of neural tube defects, cardiovascular malformations, and cleft palate due to folate antagonism; contraindicated unless no alternative. Second and third trimesters: risk of megaloblastic anemia, impaired folate metabolism; avoid if possible. Folate supplementation may reduce risk. |
| Fetal Monitoring | Monitor maternal complete blood count (CBC) including folate levels, especially in prolonged therapy; fetal ultrasound for structural anomalies if exposed in first trimester; neonatal monitoring for hyperbilirubinemia and anemia. |
| Fertility Effects | No conclusive evidence of adverse effects on fertility in humans. In animal studies, high doses have shown impaired spermatogenesis and ovarian function; clinical significance uncertain. |
| Clinical Pearls | Trimpex (trimethoprim) is a dihydrofolate reductase inhibitor primarily used for urinary tract infections. Renal dose adjustment is critical: CrCl 15-30 mL/min: reduce dose by 50%; CrCl <15 mL/min: contraindicated. Monitor for hyperkalemia, especially in elderly or those on ACE inhibitors/NSAIDs. Trimethoprim can increase serum creatinine via tubular secretion inhibition, not nephrotoxicity. Avoid in folate deficiency states (e.g., pregnancy, alcoholism). |
| Patient Advice | Take exactly as prescribed; finish the entire course even if you feel better. · May cause stomach upset; take with food or milk to reduce nausea. · Drink plenty of fluids to prevent kidney stones. · Avoid prolonged sun exposure; use sunscreen as this drug may cause photosensitivity. · Report any rash, sore throat, fever, or unusual bleeding/bruising immediately. · Do not take if you are pregnant or breastfeeding unless directed by your doctor. · Avoid potassium supplements and high-potassium foods (bananas, oranges, spinach) without medical advice. |